It is proposed that an analysis be developed for the antipsychotic agent chlorpromazine (CPZ) Thorazine R and its relatively nonpolar metabolites (chlorpromazine sulfoxide, CPZSO; mono-N-desmethylchlorpromazine, Nor1CPZ; and di-N-desmethylchlorpromazine, Nor2CPZ) in human plasma using gas-liquid chromatography with a nitrogen-sensitive detector. Use of the nitrogen-sensitive detector is expected to render excellent sensitivity as well as good precision, accuracy, and specificity to this traditionally difficult and frequently unreliable assay. These factors combined with the relative ease and inexpensiveness of the analytical system should make the assay suitable for use in the clinical laboratory. The analysis will be validated in the plasma of patients stabilized on therapeutic doses of CPZ in order to determine the therapeutic range. Plasma CPZ will also be measured in patients who have ingested an overdose of the drug, and levels will be correlated with the reported clinical findings for these patients in order to define toxic ranges. A reliable analysis for CPZ and its metabolites in plasma suitable for clinical use should permit routine therapeutic monitoring of the drug for the first tim. The measurement of serial plasma levels in overdose should provide a better understanding of the pharmacokinetics and metabolism of CPZ. The analysis may facilitate the study of the mechanism of action of CPZ, particularly when plasma CPZ is correlated with levels of the various biogenic amines and hormones that CPZ is known to affect. Such correlations should also permit further exploration of the postulated biological theories of schizophrenia.